Neuroinflammation in Sepsis: Sepsis Associated Delirium
Victoria A. McCreadie,
Sepsis-associated delirium (SAD) is a clinical manifestation of the involvement of the central nervous system
(CNS) during sepsis. The purpose of this review is to provide a concise overview of SAD including the epidemiology and
current diagnostic criteria for SAD. We present in detail the pathophysiology with regards to blood-brain-barrier
breakdown, cytokine activation and neurotransmitter deregulation. Treatment and prognosis for SAD are also briefly
discussed. SAD is the most common form of delirium acquired in the ICU (Intensive Care Unit), and is described in about
50% of septic patients. Clinical features include altered level of consciousness, reduced attention, change in cognition and
perceptual disturbances. Symptoms can reversible, but prolonged deficits can be observed in older patients. Pathophysiology
of SAD is poorly understood, but involves microvascular, metabolic and, not least, inflammatory mechanisms leading to
CNS dysfunction. These mechanisms can be different in SAD compared to ICU delirium associated with other conditions.
SAD is diagnosed clinically using validated tools such as CAM-ICU (Confusion Assessment Method for the Intensive
Care Medicine) or ICDSC (The Intensive Care Delirium Screening Checklist), which have good specificity but low
sensitivity. Neuroimaging studies and EEG (Electroencephalography) can be useful complement to clinical evaluation to
define the severity of the condition. Prompt diagnosis and eradication of septic foci whenever possible is vital. Preventive
measures for SAD in the critically ill patient requiring long-term sedation include maintaining light levels of sedation
using non-benzodiazepine sedatives (either propofol or dexmedetomidine). Early mobilization of patients in the ICU is
also recommended. Antipsychotic drugs (haloperidol and atypical antipsychotics) are widely used to treat SAD, but firm
evidence of their efficacy is lacking.
Keywords: Brain diseases, delirium, encephalopathy, neuroinflammation, sepsis, sepsis associated delirium, sepsis associated
encephalopathy, septic shock.
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